Lumbar disk degenerative disorder

Summary

Lumbar disk degenerative disorder (MONDO:0044339) is a disease with 3 cohort genes and 338 clinical trials. The dominant Reactome pathway is Collagen chain trimerization (3 cohort genes). Top therapeutic interventions include dibotermin alfa, dipyrone, and hyaluronate sodium.

At a glance

• Cohort genes: 3
• ClinVar variants: 56
• Clinical trials: 338

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lumbar disk degenerative disorder
Mondo ID	MONDO:0044339
MeSH	C535531
NCIT	C27154
SNOMED CT	26538006
UMLS	C0158252
MedGen	57852
Anatomy (UBERON)	UBERON:0006074
Is cancer (heuristic)	no

Also known as: degeneration of lumbar intervertebral disc · degeneration of lumbar intervertebral disk · degenerative disc disease · degenerative disc disorder · degenerative disk disease · degenerative disk disorder · IDD · intervertebral disc degenerative disorder of lumbar region of vertebral column · intervertebral DISC disease · intervertebral disc disease · intervertebral disc disease, susceptibility to · intervertebral disk degenerative disorder of lumbar region of vertebral column · intervertebral disk disease · intervertebral disk disease, susceptibility to · lumbar Disc Degeneration · lumbar disc degeneration, susceptibility to · lumbar Disc degenerative disease · lumbar Disc degenerative disorder · lumbar disc disease · lumbar disc disease, susceptibility to (+4 more)

Data availability: 56 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › vertebral column disorder › intervertebral disk degenerative disorder › lumbar disk degenerative disorder

Related subtypes (2): thoracic disk degenerative disorder, cervical disk degenerative disorder

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

56 retrieved; paginated sample, class counts are floors:

19 uncertain significance, 19 conflicting classifications of pathogenicity, 6 benign/likely benign, 4 likely benign, 3 pathogenic/likely pathogenic, 2 likely pathogenic, 2 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1304338	NM_001854.4(COL11A1):c.2241+5G>T	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324096	NM_001854.4(COL11A1):c.1245+1G>A	COL11A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
620141	NM_001854.4(COL11A1):c.4084C>T (p.Arg1362Ter)	COL11A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1683456	NM_001853.4(COL9A3):c.1729C>T (p.Arg577Ter)	COL9A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179083	NM_001854.4(COL11A1):c.4186G>T (p.Gly1396Cys)	COL11A1	Likely pathogenic	criteria provided, single submitter
4086151	NM_001854.4(COL11A1):c.2196+1G>A	COL11A1	Likely pathogenic	criteria provided, single submitter
1038628	NM_001854.4(COL11A1):c.3692G>T (p.Gly1231Val)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1206960	NM_001854.4(COL11A1):c.3068C>A (p.Ala1023Glu)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1314615	NM_001854.4(COL11A1):c.565C>T (p.Pro189Ser)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1357917	NM_001854.4(COL11A1):c.2285G>A (p.Arg762Gln)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1418086	NM_001854.4(COL11A1):c.4709T>C (p.Leu1570Pro)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1508766	NM_001854.4(COL11A1):c.5231A>G (p.Tyr1744Cys)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1961384	NM_001854.4(COL11A1):c.2203C>G (p.Pro735Ala)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198474	NM_001854.4(COL11A1):c.965C>T (p.Pro322Leu)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291505	NM_001854.4(COL11A1):c.4222G>A (p.Gly1408Ser)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291512	NM_001854.4(COL11A1):c.3788C>T (p.Pro1263Leu)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291526	NM_001854.4(COL11A1):c.2020C>T (p.Pro674Ser)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2976380	NM_001854.4(COL11A1):c.4186G>A (p.Gly1396Ser)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
392007	NM_001854.4(COL11A1):c.4802C>A (p.Thr1601Asn)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
985246	NM_001854.4(COL11A1):c.4213G>A (p.Gly1405Ser)	COL11A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
417900	NM_001852.4(COL9A2):c.2059A>G (p.Lys687Glu)	COL9A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1097828	NM_001853.4(COL9A3):c.387C>T (p.Ser129=)	COL9A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1221692	NM_001853.4(COL9A3):c.1918G>A (p.Glu640Lys)	COL9A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1493459	NM_001853.4(COL9A3):c.1928C>T (p.Pro643Leu)	COL9A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1506300	NM_001853.4(COL9A3):c.1851C>A (p.Asp617Glu)	COL9A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1047474	NM_001854.4(COL11A1):c.5386G>A (p.Gly1796Arg)	COL11A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1356260	NM_001854.4(COL11A1):c.549GAA[1] (p.Lys185del)	COL11A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1380051	NM_001854.4(COL11A1):c.4175C>T (p.Thr1392Ile)	COL11A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1477869	NM_001854.4(COL11A1):c.3375C>G (p.Asp1125Glu)	COL11A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1898712	NM_001854.4(COL11A1):c.2503-3T>C	COL11A1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL11A1	Orphanet:2021	Fibrochondrogenesis
COL11A1	Orphanet:440354	Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
COL11A1	Orphanet:560	Marshall syndrome
COL11A1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A1	Orphanet:90654	Stickler syndrome type 2
COL9A2	Orphanet:166002	Multiple epiphyseal dysplasia due to collagen 9 anomaly
COL9A2	Orphanet:250984	Autosomal recessive Stickler syndrome
COL9A3	Orphanet:166002	Multiple epiphyseal dysplasia due to collagen 9 anomaly
COL9A3	Orphanet:250984	Autosomal recessive Stickler syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL11A1	HGNC:2186	ENSG00000060718	P12107	Collagen alpha-1(XI) chain	clinvar
COL9A2	HGNC:2218	ENSG00000049089	Q14055	Collagen alpha-2(IX) chain	clinvar
COL9A3	HGNC:2219	ENSG00000092758	Q14050	Collagen alpha-3(IX) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL11A1	Collagen alpha-1(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
COL9A2	Collagen alpha-2(IX) chain	Structural component of hyaline cartilage and vitreous of the eye.
COL9A3	Collagen alpha-3(IX) chain	Structural component of hyaline cartilage and vitreous of the eye.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL11A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
COL9A2	Other/Unknown	no		Collagen, Collagen_superfamily
COL9A3	Other/Unknown	no		Collagen, Collagen_superfamily

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
tibia	3
cartilage tissue	2
periodontal ligament	1
C1 segment of cervical spinal cord	1
adenohypophysis	1
inferior vagus X ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL11A1	209	broad	marker	tibia, cartilage tissue, periodontal ligament
COL9A2	213	broad	marker	C1 segment of cervical spinal cord, tibia, adenohypophysis
COL9A3	218	broad	marker	tibia, cartilage tissue, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL11A1	2,433
COL9A3	1,482
COL9A2	1,419

Intra-cohort edges

A	B	Sources
COL11A1	COL9A3	string_interaction
COL9A2	COL9A3	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL9A2	Q14055	4
COL9A3	Q14050	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL11A1	P12107	53.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Collagen chain trimerization	3	259.6×	5e-07	COL11A1, COL9A2, COL9A3
Assembly of collagen fibrils and other multimeric structures	3	200.3×	5e-07	COL11A1, COL9A2, COL9A3
Collagen degradation	3	175.7×	5e-07	COL11A1, COL9A2, COL9A3
Collagen biosynthesis and modifying enzymes	3	170.4×	5e-07	COL11A1, COL9A2, COL9A3
Signaling by PDGF	2	169.2×	9e-05	COL9A2, COL9A3
NCAM1 interactions	2	165.5×	9e-05	COL9A2, COL9A3
ECM proteoglycans	2	100.2×	2e-04	COL9A2, COL9A3
Integrin cell surface interactions	2	89.6×	2e-04	COL9A2, COL9A3
MET activates PTK2 signaling	1	126.9×	0.010	COL11A1
Developmental Lineage of Pancreatic Ductal Cells	1	76.1×	0.014	COL11A1
Non-integrin membrane-ECM interactions	1	51.4×	0.019	COL11A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
tendon development	1	2106.5×	0.006	COL11A1
proteoglycan metabolic process	1	936.2×	0.006	COL11A1
chondrocyte development	1	468.1×	0.006	COL11A1
detection of mechanical stimulus involved in sensory perception of sound	1	468.1×	0.006	COL11A1
cartilage condensation	1	383.0×	0.006	COL11A1
ventricular cardiac muscle tissue morphogenesis	1	351.1×	0.006	COL11A1
endodermal cell differentiation	1	247.8×	0.007	COL11A1
embryonic skeletal system morphogenesis	1	195.9×	0.008	COL11A1
inner ear morphogenesis	1	150.5×	0.010	COL11A1
collagen fibril organization	1	112.3×	0.012	COL11A1
skeletal system development	1	62.9×	0.019	COL9A2
sensory perception of sound	1	50.5×	0.021	COL11A1
visual perception	1	39.8×	0.025	COL11A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL11A1	0	0
COL9A2	0	0
COL9A3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	COL11A1, COL9A2, COL9A3

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COL11A1	0	—
COL9A2	0	—
COL9A3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 338.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	267
PHASE3	17
PHASE1/PHASE2	16
PHASE4	14
PHASE2	13
PHASE1	10
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03060434	PHASE4	ACTIVE_NOT_RECRUITING	Pentoxifylline and Lumbar Radiculopathy
NCT05029726	PHASE4	RECRUITING	Regional Anesthesia in Minimally Invasive Lumbar Spine Surgery
NCT00165893	PHASE4	COMPLETED	Comparison of IDD Therapy and Non-surgical Treatment for Low Back Pain Caused by Degenerative Disc Disease
NCT01502644	PHASE4	COMPLETED	Opioid Treatment for Chronic Low Back Pain and the Impact of Mood Symptoms
NCT02429908	PHASE4	COMPLETED	Post-Market Surveillance Study of the TM Ardis Interbody Fusion System
NCT03077204	PHASE4	COMPLETED	BIO4 Clinical Case Study: Cervical Spine
NCT03223701	PHASE4	WITHDRAWN	Efficacy of Using Solum IV and BMC With GFC in TLIF
NCT03514277	PHASE4	TERMINATED	A Prospective Study to Compare Bupivacaine and Exparel Versus Bupivacaine or Exparel Alone for Postoperative Pain Relief
NCT03745040	PHASE4	SUSPENDED	Liposomal Bupivacaine in One-level Instrumented Posterior Spinal Fusion
NCT03751943	PHASE4	UNKNOWN	NanoFUSE® PL Gutter PMCF
NCT04734327	PHASE4	UNKNOWN	Orthokine Therapy in Lumbar Degenerative Disease
NCT05247021	PHASE4	UNKNOWN	Erector Spinae Plane Block in Spine Surgeries
NCT05345249	PHASE4	COMPLETED	Erector Spinae Plane Block as Pain Management After Lumbar Fusion Surgery
NCT06034041	PHASE4	UNKNOWN	The Effect of Mediclore as an Anti-adhesion Agent and Safety in Full-endoscopic Spine Surgery: a Preliminary Study
NCT03737461	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Efficacy of Intradiscal Injection of BM-MSC in Subjects With Chronic Low Back Pain (LBP) Due to Lumbar Degenerative Disc Disease (DDD) Unresponsive
NCT05444751	PHASE3	ENROLLING_BY_INVITATION	GA + ESP vs. SA + ESP in Lumbar Decompression Surgeries
NCT06115512	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study of AGA111 in Patients With Degenerative Disc Disease Undergoing Lumbar Interbody Fusion
NCT06325566	PHASE3	RECRUITING	Efficacy and Safety of Rexlemestrocel-L Combined With HA* in Participants With Moderate to Severe Chronic Low Back Pain
NCT07017634	PHASE3	RECRUITING	Efficacy and Safety of Novosis Putty in Transforaminal Lumbar Interbody Fusion for Patients With Lumbar Degenerative Disc Disease
NCT07254806	PHASE3	RECRUITING	A Study to Evaluate the Effectiveness of IDCT (Intradiscal Cell Therapy) in Subjects With One Level, Symptomatic Mild to Moderate Lumbar Degenerative Disc Disease
NCT00215306	PHASE3	COMPLETED	CHARITÉ™ Artificial Disc Compared to Anterior Interbody Fusion for Treatment of Degenerative Disc Disease
NCT00215319	PHASE3	COMPLETED	Titanium Surgical Mesh and MOSS-Miami Screws for Lumbar Fusion.
NCT00316121	PHASE3	COMPLETED	Safety and Efficacy Study of Healos as a Bone Replacement to Treat Degenerative Disc Disease
NCT00707265	PHASE3	COMPLETED	rhBMP-2/CRM/CD HORIZON® Spinal System Pivotal Study
NCT00927238	PHASE3	COMPLETED	XL TDR® eXtreme Lateral Total Disc Replacement for the Treatment of Lumbar Degenerative Disc Disease (DDD)
NCT01011816	PHASE3	TERMINATED	Treatment of Symptomatic Lumbar Internal Disc Disruption (IDD) With the Biostat® System
NCT01941563	PHASE3	COMPLETED	A Study of SI-6603 in Patients With Lumbar Disc Herniation
NCT02412735	PHASE3	COMPLETED	Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Participants With Chronic Low Back Pain
NCT02421601	PHASE3	COMPLETED	A Study of SI-6603 in Patients With Lumbar Disc Herniation
NCT03327272	PHASE3	WITHDRAWN	Impact of Local Steroid Application in Extreme Lateral Lumbar Interbody Fusion
NCT03513445	PHASE3	WITHDRAWN	Peri-Incisional Drug Injection in Lumbar Spine Surgery
NCT04816747	PHASE3	UNKNOWN	Intradiscal and Intra-articular Injection of Autologous Platelet-Rich-Plasma (PRP) in Patients With Lumbar Degenerative Disc Disease and Facet Joint Syndrome
NCT04042844	PHASE2	RECRUITING	A Single Dose of BRTX 100 for Patients With Chronic Lumbar Disc Disease (cLDD)
NCT06053242	PHASE1/PHASE2	RECRUITING	Safety, Tolerability, and Effectiveness of Intramuscular Injection of CELZ-201-DDT for the Treatment of Chronic Lower Back Pain
NCT06462729	PHASE1/PHASE2	RECRUITING	LDGraft in Single Level Anterior Lumbar Interbody Fusion (ALIF)
NCT06615505	PHASE2	ACTIVE_NOT_RECRUITING	ASCEND: A Clinical Trial to Evaluate the Safety and Effectiveness of VIA Disc NP, a Supplement for Degenerated Intervertebral Discs
NCT00549913	PHASE1/PHASE2	COMPLETED	Study of 3 Doses of NeoFuse Combined With MasterGraft Granules in Subjects Requiring Posterolateral Lumbar Fusion (PLF)
NCT00798239	PHASE1/PHASE2	UNKNOWN	Pilot Study to Assess Safety/Prelimary Effectiveness of Prefix in Subjects With Degenerative Disc Disease (DDD) Undergoing Spine Fusion Surgery
NCT00798902	PHASE1/PHASE2	UNKNOWN	Pilot Study to Assess Safety/Preliminary Effectiveness of Prefix in Subjects With Degenerative Disc Disease (DDD) Undergoing Spine Fusion Surgery
NCT00810212	PHASE1/PHASE2	WITHDRAWN	Safety and Efficacy Study of NeoFuse in Subjects Requiring Posterolateral Lumbar Fusion

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DIBOTERMIN ALFA	4	13
DIPYRONE	4	1
HYALURONATE SODIUM	4	1
IBUPROFEN	4	1
MEPIVACAINE	4	1
METHADONE HYDROCHLORIDE	4	1
MORPHINE	4	1
OXYCODONE	4	1
PENTOXIFYLLINE	4	1
ROPIVACAINE	4	1
WATER	4	1
REXLEMESTROCEL-L	3	3
CONDOLIASE	3	2
ESMETHADONE	3	1
LORECIVIVINT	3	1
RADOTERMIN	2	4
RACEPINEPHRINE	2	1
REBONUPUTEMCEL	1	3
CHEMBL4589226	0	2